Amine oxidase (copper-containing) explained

amine oxidase
Ec Number:	1.4.3.6
Cas Number:	9001-53-0
Go Code:	0008131

Symbol:	Cu_amine_oxidN1
Copper amine oxidase N-terminal domain
Pfam:	PF07833
Interpro:	IPR012854
Scop:	1spu

Symbol:	Cu_amine_oxidN2
Copper amine oxidase, N2 domain
Pfam:	PF02727
Pfam Clan:	CL0047
Interpro:	IPR015800
Prosite:	PDOC00895
Scop:	1oac

Symbol:	Cu_amine_oxidN3
Copper amine oxidase, N3 domain
Pfam:	PF02728
Pfam Clan:	CL0047
Interpro:	IPR015802
Prosite:	PDOC00895
Scop:	1oac

Amine oxidase (copper-containing) (AOC) (and ; formerly) is a family of amine oxidase enzymes which includes both primary-amine oxidase and diamine oxidase; these enzymes catalyze the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. They act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor:^[1]

RCH₂NH₂ + H₂O + O₂

\rightleftharpoons RCHO + NH₃ + H₂O₂

The 3 substrates of this enzyme are primary amines (RCH2NH2), H₂O, and O₂, whereas its 3 products are RCHO, NH₃, and H₂O₂.

Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen.^{[2] [3]}

This enzyme belongs to oxidoreductases, specifically those acting on the CH-NH2 group of donors with oxygen as acceptor. The systematic name of this enzyme class is amine:oxygen oxidoreductase (deaminating) (copper-containing). This enzyme participates in 8 metabolic pathways: urea cycle and metabolism of amino groups, glycine, serine and threonine metabolism, histidine metabolism, tyrosine metabolism, phenylalanine metabolism, tryptophan metabolism, beta-alanine metabolism, and alkaloid biosynthesis ii. It has 2 cofactors: copper, and PQQ.

Structure

The copper amine oxidase 3-dimensional structure was determined through X-ray crystallography.The copper amine oxidases occur as mushroom-shaped homodimers of 70-95 kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a beta sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access.

The N2 and N3 N-terminal domains share a common structural fold, its core consisting of alpha-beta(4), where the helix is packed against the coiled anti-parallel beta-sheets. An additional domain is found at the N-terminal of some copper amine oxidases, as well as in related proteins such as cell wall hydrolase and N-acetylmuramoyl-L-alanine amidase. This domain consists of a five-stranded antiparallel beta-sheet twisted around an alpha helix.^{[4] [5]}

Function

In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling;^[6] one AOC enzyme (AOC3) functions as a vascular adhesion protein (VAP-1) in some mammalian tissues.

Human proteins containing this domain

• AOC1
• AOC2
• AOC3

See also

• Copper in health

Further reading

• Ameyama M, Hayashi M, Matsushita K, Shinagawa E, Adachi O . 1984 . Microbial-production of pyrroloquinoline quinone . Agric. Biol. Chem. . 48 . 2 . 561 - 565 . 10.1271/bbb1961.48.561. free .
• Augustinsson KB, Olsson B . 1959 . Esterases in the milk and blood plasma of swine. I. Substrate specificity and electrophoresis studies . Biochem. J. . 71 . 477 - 84 . 13638253 . 3 . 1196820 . 10.1042/bj0710477 .
• Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 8, Academic Press, New York, 1963, p. 337-351.
• Buffoni F, Blaschko H . 1964 . Benzylamine oxidase and histaminase: purification and crystallization of an enzyme from pig plasma . . 161 . 983 . 153 - 67 . 14224405 . 10.1098/rspb.1964.0086 . 1964RSPSB.161..153B . 43432156 .
• Haywood GW, Large PJ . 1981 . Microbial oxidation of amines. Distribution, purification and properties of two primary-amine oxidases from the yeast Candida boidinii grown on amines as sole nitrogen source . Biochem. J. . 199 . 187 - 201 . 7337701 . 1 . 1163349 . 10.1042/bj1990187.
• McEwen CM Jr . 1965 . Human plasma monoamine oxidase. 1. Purification and identification . J. Biol. Chem. . 240 . 2003 - 10 . 5888801 . 5 .
• Mondovi B, Costa MT, Agro AF, Rotilio G . 1967 . Pyridoxal phosphate as a prosthetic group of pig kidney diamine oxidase . Arch. Biochem. Biophys. . 119 . 373 - 81 . 4964016 . 10.1016/0003-9861(67)90468-7 . 1 .
• Yamada H, Adachi O, Ogata K . 1965 . Amine oxidases of microorganisms. Part II. Purification and crystallisation of amine oxidase of Aspergillus niger . Agric. Biol. Chem. . 29 . 649 - 654 . 10.1271/bbb1961.29.649 . free .
• Yamada H, Adachi O, Ogata K . 1965 . Amine oxidases of microorganisms. Part III. Properties of amine oxidase of Aspergillus niger . Agric. Biol. Chem. . 29 . 864 - 869 . 10.1271/bbb1961.29.864 . free .
• Yamada H, Adachi O, Ogata K . 1965 . Amine oxidases of microorganisms. Part IV. Further properties of amine oxidase of Aspergillus niger . Agric. Biol. Chem. . 29 . 912 - 917 . 10.1271/bbb1961.29.912 . free .
• Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 8, Academic Press, New York, 1963, p. 313-335.

Notes and References

1. Convery MA, Phillips SE, McPherson MJ, Yadav KD, Knowles PF, Parsons MR, Wilmot CM, Blakeley V, Corner AS . Crystal structure of a quinoenzyme: copper amine oxidase of Escherichia coli at 2 A resolution . Structure . 3 . 11 . 1171–1184 . 1995 . 8591028 . 10.1016/s0969-2126(01)00253-2. free .
2. Murray JM, Convery MA, Phillips SE, McPherson MJ, Knowles PF, Parsons MR, Wilmot CM, Blakeley V, Corner AS, Alton G, Palcic MM . Catalytic mechanism of the quinoenzyme amine oxidase from Escherichia coli: exploring the reductive half-reaction . Biochemistry . 36 . 7 . 1608–1620 . 1997 . 9048544 . 10.1021/bi962205j.
3. Tanizawa K, Guss JM, Freeman HC, Yamaguchi H, Wilce MC, Dooley DM, Matsunami H, Mcintire WS, Ruggiero CE . Crystal structures of the copper-containing amine oxidase from Arthrobacter globiformis in the holo and apo forms: implications for the biogenesis of topaquinone . Biochemistry . 36 . 51 . 16116–16133 . 1997 . 9405045 . 10.1021/bi971797i.
4. Parsons MR, Convery MA, Wilmot CM, Yadav KD, Blakeley V, Corner AS, Phillips SE, McPherson MJ, Knowles PF . Crystal structure of a quinoenzyme: copper amine oxidase of Escherichia coli at 2 A resolution . Structure . 3 . 11 . 1171–84 . November 1995 . 8591028 . 10.1016/s0969-2126(01)00253-2. free .
5. Wilmot CM, Hajdu J, McPherson MJ, Knowles PF, Phillips SE . Visualization of dioxygen bound to copper during enzyme catalysis . Science . 286 . 5445 . 1724–8 . November 1999 . 10576737 . 10.1126/science.286.5445.1724 .
6. Guss JM, Freeman HC, Kumar V, Wilce MC, Dooley DM, Harvey I, Mcguirl MA, Zubak VM . Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution . Structure . 4 . 8 . 943–955 . 1996 . 8805580 . 10.1016/s0969-2126(96)00101-3. free .